Interleukin-2 receptor alpha-chain (CD25) expression on leukaemic blasts is predictive for outcome and level of residual disease in AML

Terwijn, Monique; Feller, N; Rhenen, Anna van; Kelder, Angèle; Westra, Guus; Zweegman, Sonja; Ossenkoppele, Gert J.; Schuurhuis, Gerrit Jan

doi:10.1016/j.ejca.2009.02.021

Cited by 65 publications

(63 citation statements)

References 32 publications

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“…In accordance with previous observations, 22,23 we found a high frequency of FLT3-ITD POS cases in CD25 POS AML (76% of cases), but we failed to confirm an association of CD25 expression with the putative stem cell markers CD34, CD133, or P-glycoprotein. In addition, CD25 POS cases failed to demonstrate immunophenotypic features of undifferentiated (CD65 NEG ) AML more frequently than CD25 NEG cases.…”

Section: Discussionsupporting

confidence: 85%

“…Terwijn et al reported that minimal residual disease levels after induction chemotherapy were significantly greater in CD25 POS than CD25 NEG AML. 22 Similarly, the presence of a high frequency of LSCs at diagnosis has been correlated with high levels of minimal residual disease after chemotherapy. 42 We hypothesize that CD25 expression in AML serves as a surrogate for the presence of chemoresistant LSCs.…”

Section: Discussionmentioning

confidence: 99%

“…Previously published data from small retrospective studies have suggested an unfavorable impact of CD25. [21][22][23] In the largest group studied to date, 22 CD25 was an independent adverse factor for the achievement of complete remission (CR), OS, and relapse-free survival in 65 patients with AML who were Յ 60 years of age treated on protocols from the Hemato-Oncologie voor Volwassenen Nederland (HOVON) or Haemato Oncology Foundation for Adults in The Netherlands. CD25 expression was positively associated with the presence of internal tandem duplications in FLT3 (FLT3-ITD), 22,23 a known adverse prognostic factor in AML, 24 suggesting that CD25 might function as a surrogate marker for FLT3-ITD.…”

Section: Introductionmentioning

confidence: 99%

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CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900

Gönen

Sun

Figueroa

et al. 2012

Blood

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We determined the prognostic relevance of CD25 (IL-2 receptor-␣) expression in 657 patients (< 60 years) with de novo acute myeloid leukemia (AML) treated in the Eastern Cooperative Oncology Group trial, E1900. We identified CD25 POS myeloblasts in 87 patients (13%), of whom 92% had intermediate-risk cytogenetics. CD25 expression correlated with expression of stem cell antigen CD123. In multivariate analysis, controlled for prognostic baseline characteristics and daunorubicin dose, CD25 POS patients had inferior complete remission rates (P ‫؍‬ .0005) and overall survival (P < .0001) compared with CD25 NEG cases. In a subset of 396 patients, we integrated CD25 expression with somatic mutation status to determine whether CD25 impacted outcome independent of prognostic mutations. CD25 was positively correlated with internal tandem duplications in FLT3 (FLT3-ITD), DNMT3A, and NPM1 mutations. The adverse prognostic impact of FLT3-ITD POS AML was restricted to CD25 POS patients. CD25 expression improved AML prognostication independent of integrated, cytogenetic and mutational data, such that it reallocated 11% of patients with intermediate-risk disease to the unfavorable-risk group. Gene expression analysis revealed that CD25 POS status correlated with the expression of previously reported leukemia stem cell signatures. We conclude that CD25 POS status provides prognostic relevance in AML independent of known biomarkers and is correlated with stem cell gene-expression signatures associated with adverse outcome in AML. (Blood. 2012;120(11):2297-2306) IntroductionIncreasingly, recurrent genetic aberrations govern the prognostication of the acute leukemias, including the large group of patients who present with acute myeloid leukemia (AML) without apparent cytogenetic abnormalities. A steadily growing catalog of molecular lesions has led to the development of outcome-based classification systems that incorporate information on perturbed pathogenetic pathways and inform us about potential therapeutic targets. [1][2][3][4] In the context of this evolving molecular risk assessment, antigenexpression profiles have been identified as surrogates for certain leukemic genotypes. Furthermore, a few single antigens per se have been found to be predictive of clinical response. In most cases, however, the prognostic power of antigens has not been disassociated from underlying genetic determinants.The prognostic impact of antigens, such as CD1a and CD13, in T-lineage acute lymphoblastic leukemia (ALL) 5 has been linked to molecular subgroups with the activation of specific transcription factors and with unique gene expression signatures, reflecting distinct stages of maturation. 6 In acute promyelocytic leukemia (APL), expression of the T cell-affiliated antigen, CD2, in association with S-isoform PML/RAR␣, 7 confers inferior prognosis. 8 CD2 POS S-isoform POS APL is distinguishable from other isoforms on the basis of gene-expression profiling (GEP) 9 and has been posited to be derived from an immature leukemia stem cell (LSC). 10 Su...

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900

Gönen

Sun

Figueroa

et al. 2012

Blood

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“…Regarding functional investigation of CD25, the authors reported that CD34 þ CD38-CD25 þ AML cells engrafted in all four recipients evaluated, but did not mention results of engraftment studies conducted with CD34 þ CD38-CD25À cells. Notably, CD25 expression has recently been reported to be an adverse prognostic factor when expressed on greater than 10% of AML blasts, and its expression correlated with minimal residual disease (Terwijn et al, 2009). In the final experiments investigating CD32 and CD25, expression of these antigens on normal cells and tissues was reported (Saito et al, 2010).…”

Section: Human Aml Stem Cellsmentioning

confidence: 99%

Monoclonal antibody therapy directed against human acute myeloid leukemia stem cells

2010

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“…Jan Cerny, 2013 stated that over expression of CD25 was a strong predictor of induction failure and relapse. Terwijn l 2009 reported that over CD25 expression (>10%) in young AML patients (<60 years) in retrospective study associated with a significant shorter survival and relapse free survival [30].…”

Section: Discussionmentioning

confidence: 99%

Methylated SFRP1,2 and CD25 Expression in Acute Myeloid Leukemia Play an Important Role in the Pathogenesis of the Disease and in Turn in its Treatment

Elrahman¹,

Nigm²,

Elfadle³

2016

J Leuk

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Twenty five healthy persons as a negative control group and 40 patients with de novo AML were involved in this study. These patients were admitted to Hematology unit, clinical pathology department and south Egypt cancer institute, Assiut University, Egypt, and were grouped depending on morphology and immune phenotyping (FAB classification).The clinical data consisted of age and sex, laboratory data consisted of hemoglobin level, white blood cell count, platelets count and the recovery after induction chemotherapy were taken from patients' medical records. Flowcytometric analysisA panel of monoclonal antibodies was designed against myeloid lineage specific antigens including CD13, CD33, MPO, Cyto MPO,

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Interleukin-2 receptor alpha-chain (CD25) expression on leukaemic blasts is predictive for outcome and level of residual disease in AML

Cited by 65 publications

References 32 publications

CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900

CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900

Monoclonal antibody therapy directed against human acute myeloid leukemia stem cells

Methylated SFRP1,2 and CD25 Expression in Acute Myeloid Leukemia Play an Important Role in the Pathogenesis of the Disease and in Turn in its Treatment

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